Micronutrients present in edible plants are known to possess anti-carcinogenic properties because epidemiological studies have suggested that consumption of fruits and vegetables may prevent against many cancer types. This approach of chemoprevention of cancer has practical implications in reducing cancer risk because unlike the carcinogenic environmental factors that are difficult to control, individuals can make decisions to modify their choice for the food and beverage they consume. Tea, a preparation from the dried leaves of Camellia sinensis, is a widely and popularly consumed beverage in the world. Extensive studies from several laboratories over the last ten years, have verified cancer chemopreventive effects of a polyphenolic mixture derived from green tea [hereafter referred to as green tea polyphenols (GTP)] in many animal tumor bioassay systems. However, the anticarcinogenic potential of green tea against hard tissue tumors (osteosarcomas or chondrosarcomas) has not been extensively explored. We have found that GTP induce apoptosis in osteosarcoma cells SA-OS2. The central hypothesis to be tested in this proposal is that green tea induce apoptosis in osteosarcoma cells by modulating the cell cycle- and apoptotic- machinery of SA-OS2 cells. Therefore, in this developmental application we will explore these phenomenon further by determining (1) whether GTP induce apoptosis in SA-OS2 cells by modulating the constitutively active NF-KappaB; (2) whether GTP induce apoptosis in SA-OS2 cells through cell cycle arrest by up-regulating the expression of p21; and (3) whether GTP induce apoptosis in SA-OS2 cells by altering the Bax/Bcl2 ratio. Successful completion of this project will establish the role of green tea against Osteosarcomas and may also help in the development of novel preventive approaches against hard tissue tumors in man.